Legal and ethical issues in the international transaction of donor sperm and eggs

Pertinent ethical and legal issues in the international transaction of donor sperm and eggs are discussed. Firstly, there may be legislative and ethical “contradiction” by the local health authority in permitting import of donor gametes, due to varying policies on donor reimbursement in different countries. This is particularly significant in countries where the underlying principle of gamete donation is altruistic motivation, and where reimbursement is given only for direct “out-of-pocket” expenses i.e. traveling costs. Secondly, there is a lack of clear and coherent internationally-binding legislation and regulatory guidelines overseeing the exchange of donor gametes across international borders. In particular, provisions should be made for donor traceability if gametes are sourced from abroad. Thirdly, in the case of “frozen-egg donation” from abroad, patients must rightfully be informed that current cryopreservation technology is still sub-optimal, and all studies have consistently shown that the chances of conception are always lower with “frozen-eggs” compared to freshly-retrieved eggs. Finally, regulatory safeguards should be put in place to prevent fertility clinics and medical professionals from “re-selling” imported donor gametes at a profit to the patient, since it would be thoroughly unprofessional for them to earn a profit simply through the ‘brokerage’ of donated human material.     

Angiogenesis in implantation

Problem Implantation failure and early pregnancy loss are common following natural conceptions and they are particularly important clinical hurdles to overcome following assisted reproduction attempts. The importance of adequate vascular development and maintenance during implantation has recently become a major focus of investigation. Materials and methods Review of current published literature was undertaken to summerize the cells and cell products that regulate tissue vascularity during implantation. Results Vascular development at the maternal fetal interface can be regulated by a number of different cell types; two principal candidates are trophoblast and natural killer cells. A wide range of soluble factors, some with well established angiogenic functions as well as other more novel factors, can contribute to vascular development and maintenance at the maternal–fetal interface. Conclusions Robust vascular development occurs during implantation and early placentation of normal pregnancies. Studies to define the extent and mechanisms by which defects in vascularity contribute to human implantation failure and early miscarriage need to be undertaken. Vascular development during implantation is mediated by numerous cell types and cell products and aberrant vascularity likely contributes to implantation failure and early pregnancy loss.     

Cytokines: Important for implantation?

Problem

Cytokines are obviously very important in an established pregnancy, but what about human embryo implantation?

Methods

Literature review.

Results

We first discuss the necessity and limits of animal models, and then review the few cytokines which have been demonstrated by knock-out methods to be absolutely necessary for embryo implantation using in animal models. We then review what is known or discussed about the role of other cytokines as deduced from quantitative and/or qualitative dysregulation in animals and in humans.

Conclusions

Cytokines are indeed involved in implantation as they are in ongoing pregnancy and delivery. Relevance to infertility and recurrent pregnancy loss is discussed.     

Analysis of meiotic segregation patterns and interchromosomal effects in sperm from six males with Robertsonian translocations

Purpose To provide more genetic information about meiotic segregation behavior and the possibility of interchromosomal effects (ICE) in spermatozoa from carriers of Robertsonian (Rob) translocations. Materials and methods Meiotic segregation behavior in spermatozoa from six carriers of Rob translocations, four t(13;14), one t(14;22) and one t(13;21), was investigated by dual fluorescence in-situ hybridization (FISH). Aneuploidy for chromosomes 18, X and Y was studied by triple FISH. Results The rate of normal/balanced spermatozoa resulting from alternate segregation ranged from 78.14 to 86.88%. The frequency of unbalanced spermatozoa resulting from adjacent segregation varied between 11.70 and 19.53%. The higher frequencies of aneuploidy for sex chromosome were observed in three Rob translocation carriers. In addition, the increased rates of diploid were found in two t(13;14) carriers. Conclusions Alternate segregation is dominant in the different types of Rob translocations. Some carriers may be at an increased risk for ICE. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users. An increased aneuploidy for sex chromosome observed in three Robertsonian translocation carriers suggests that an interchromosomal effect is likely in some carriers.     

Silver-Russell syndrome in a girl born after <Emphasis Type="Italic">in vitro</Emphasis> fertilization: partial hypermethylation at the differentially methylated region of <Emphasis Type="Italic">PEG1</Emphasis>/<Emphasis Type="Italic">MEST</Emphasis>

Purpose: The prevalence of low birth weight (LBW) is increased in subjects born after assisted reproduction technology (ART), and defective imprinting has frequently been identified in patients with Beckwith-Wiedermann and Angelman syndromes conceived by ART. Thus, we examined methylation pattern in a girl born after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal uniparental disomy for chromosome 7 and by hypomethylation of the differentially methylated region (DMR) of H19. Methods: We examined methylation status of 31 cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23 cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte genomic DNA. Results: Eight of the 31 cytosines in the patient and four of the 31 cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19-DMR, no abnormal methylation pattern was identified in the patient. Conclusion: The results suggest that hypermethylation of paternally expressed genes including PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in subjects conceived by ART. Partial hypermethylation was identified at the differentially methylated region of paternally expressed PEG1/MEST in a girl with Silver-Russell syndrome born after in vitro fertilization.     

Cumulative exposure to high estradiol levels during the follicular phase of IVF cycles negatively affects implantation

Purpose: To investigate the effect of the cumulative exposure to estradiol (E₂) during the follicular phase on IVF outcome. Methods: Patients were stimulated with recombinant FSH after GnRH agonist suppression and had a day 3-embryo transfer. Estrogen exposure was determined as the area under the curve (AUC) for serum E₂ levels measured from the first day of stimulation through the day after hCG administration. Results: E₂ AUC thresholds for 10th and 90th percentiles were 4704 pg/ml and 16338 pg/ml, respectively. The pregnancy and implantation rates were highest in the 10th–90th percentile group, and were statistically higher in this group than in the >90th percentile group (54.6% vs. 33.3% and 24.8% and 12.9%, respectively, for pregnancy and implantation rates, P < 0.05). Recovered mature oocytes, fertilization, and number and mean score of transferred embryos were similar. Conclusions: High cumulative E₂ exposure during the follicular phase of IVF cycles has detrimental effects on implantation.     

Too old for IVF: are we discriminating against older women?

In vitro fertilization (IVF) in women of advanced age (>42 years) represents only 5%, a comparatively minute part, of the national IVF experience in the United States (US). In view of evolving population dynamics, it, however, also represents proportionally a rather quickly expanding patient need. Because of access restrictions at many IVF programs, this market does not live up to its potential. As best demonstrated by the 2004 US National Summary and Fertility Clinic Report, which for the first time reported pregnancies and births above age 45 year, IVF in women of advanced reproductive age represents a cutting edge area of interest for improving current IVF outcomes. Access to IVF should, therefore, not be withheld based on female age and/or baseline FSH levels. Instead, a definition of acceptable minimal pregnancy and life birth rates could be used to define the limits of offered access to IVF, independent of age and/or baseline FSH levels.     

The possible role of hyperhomocysteinemia on IVF outcome

Purpose To evaluate the effect of the hyperhomocysteinemia on pregnancy rate, implantation rate and abortion rate after IVF. Method Data from a total of 48 infertile couples with hyperhomocysteinemia were prospectively collected for this study. All patients underwent a standard down regulation protocol for ovarian stimulation. Oocytes recovery was performed at 36 h after hCG administration. Embryo transfer took place at 48 h after insemination. The patients were matched in two groups that received or did not receive therapy (group A and B respectively) to normalize homocysteine plasma level. Results Pregnancy rate, implantation rate and abortion rate varied significantly (p ≤ 0.05) between the two groups. The number and quality of embryos transferred did not differ between the groups. Conclusion The results suggest that hyperhomocysteinemia could affect IVF outcome     

A normal birth following preimplantation genetic diagnosis by FISH determination in the carriers of der(15)t(Y;15)(Yq12;15p11) translocations: two case reports

Purpose To investigate the clinical application of fluorescence in situ hybridization (FISH) for assessing chromosome disorders of embryos in preimplantation diagnosis of carriers with der(15)t(Y;15)(q12;p11) translocations. Methods Multicolor FISH was performed using directly-labelled DNA probes, chromosome X with one (DXZ1, Xp11.1-q11.1), but Y with two (DYZ3, Yp11.1-q11.1 and DYZ1, Yq12). Normal embryos were transferred on day 6 at blastocyst stage. Results Couple A: Three of 6 biopsied embryos were normal. Two normal blastocysts were transferred, but no pregnancy was achieved. Couple B: Three of 6 biopsied embryos were normal. Two normal blastocysts were transferred. A normal male infant weighing 3,230 g was born by cesarean section on the 39th week of gestation. All of the remaining nonreplaced embryos showed mosaic or der(15). Conclusion Embryos from carries of der(15)t(Y;15)(q12;p11) translocation showed a high frequency of chromosome abnormalities. PGD is a valuable screen tool for those couples to treat their infertility and break the transmission of der(15) chromosome for their offspring.